Phase separation of RNA-binding protein promotes polymerase binding and transcription

Wen Shao, Xianju Bi, Yixuan Pan, Boyang Gao, Jun Wu, Yafei Yin, Zhimin Liu, Mengyuan Peng, Wenhao Zhang, Xu Jiang, Wenlin Ren, Yanhui Xu, Zhongyang Wu, Kaili Wang, Ge Zhan, J. Yuyang Lu, Xue Han, Tong Li, Jianlong Wang, Guohong LiHaiteng Deng, Bing Li, Xiaohua Shen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

An RNA-involved phase-separation model has been proposed for transcription control. However, the molecular links that connect RNA to the transcription machinery remain missing. Here we find that RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), some being colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs show that the paraspeckle protein PSPC1 inhibits the RNA-induced premature release of Pol II, and makes use of RNA as multivalent molecules to enhance the formation of transcription condensates and subsequent phosphorylation and release of Pol II. This synergistic interplay enhances polymerase engagement and activity via the RNA-binding and phase-separation activities of PSPC1. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II binding and nascent transcription. We propose that promoter-associated RNAs and their binding proteins synergize the phase separation of polymerase condensates to promote active transcription. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalNature Chemical Biology
Volume18
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

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